Alcoholism is a complex condition in which there are many potential molecular and therapeutic targets for pharmacotherapy. This fast track SBIR contract aims to investigate compounds targeted on the glutamate/NMDA receptor (NMDAR) and the nicotinic receptor for acetylcholine (nicAChR). These targets have direct relevance to several of the major therapeutic targets including detoxification of acute withdrawal, neurotoxicity, relapse, organ damage, co-morbid neuropathic pain, and co-morbid drug abuse (including smoking). Naprogenix first identifies synthetic drugs or plant metabolites by high throughput pharmacological screening, prioritizing lead compounds which have valuable multifunctionality. Leads are then tested in whole animal screens and models reflecting different specific aspects of alcoholism and the most promising are optimized by synthetic modification, or by a novel plant genomic approach. Phase 1 of this fast track proposal is to complete preliminary studies at the molecular level on the 4 current best therapeutic candidates (2 synthetics and 2 natural products), and to prepare sufficient quantities of these for cellular studies and whole animal evaluation in phase 2. Also during phase 2, the company, with the National Institute on Alcohol Abuse and Alcoholism (NIAAA), will contact major pharmaceutical and nutritional companies to explore the further development of these compounds as medications or nutraceuticals.